For over a hundred years, X‐rays have been a main component of the radiotherapeutic approaches to treat cancer. Yet, to date, no radiosensitizer has been developed to selectively target prostate cancer. Gold has excellent X‐ray absorptivity and is used as a radiotherapy enhancing material. In this work, ultrasmall Au25 nanoclusters (NCs) are developed for selective prostate cancer targeting, radiotherapy enhancement, and rapid clearance from the body. Targeted‐Au25 NCs are rapidly and selectively taken up by prostate cancer in vitro and in vivo and also have fast renal clearance. When combined with X‐ray irradiation of the targeted cancer tissues, radiotherapy is significantly enhanced. The selective targeting and rapid clearance of the nanoclusters may allow reductions in radiation dose, decreasing exposure to healthy tissue and making them highly attractive for clinical translation.

Prostate-Specific Membrane Antigen (PSMA) targeted radiosensitizers are developed for prostate cancer CT imaging and radiotherapy based on gold nanoparticles and a high-affinity targeting peptide, PSMA-1, revealing a size-dependent pattern.

Skeletal muscles undergo atrophy in response to diseases and aging. Here we report that mitofusin 2 (Mfn2) acts as a dominant suppressor of neuromuscular synaptic loss to preserve skeletal muscles. Mfn2 is reduced in spinal cords of transgenic SOD1 and aged mice. Through preserving neuromuscular synapses, increasing neuronal Mfn2 prevents skeletal muscle wasting in both SOD1 and aged mice, whereas deletion of neuronal Mfn2 produces neuromuscular synaptic dysfunction and skeletal muscle atrophy. Neuromuscular synaptic loss after sciatic nerve transection can also be alleviated by Mfn2. Mfn2 coexists with calpastatin largely in mitochondria-associated membranes (MAMs) to regulate its axonal transport. Genetic inactivation of calpastatin abolishes Mfn2-mediated protection of neuromuscular synapses. Our results suggest that, as a potential key component of a novel and heretofore unrecognized mechanism of cytoplasmic protein transport, Mfn2 may play a general role in preserving neuromuscular synapses and serve as a common therapeutic target for skeletal muscle atrophy.

Inclusion body myositis (IBM) is the most common cause of primary myopathy in individuals ages 50 years and over, and is pathologically characterized by protein aggregates of p62 and mislocalized cytoplasmic TDP-43 as well as mitochondrial abnormalities in affected muscle fibers. Our recent studies have shown the accumulation of TDP-43 in mitochondria in neurons from patients with amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), and revealed mitochondria as critical mediators of TDP-43 neurotoxicity. In this study, we investigated the association between mitochondria and TDP-43 in biopsied skeletal muscle samples from IBM patients. We found that IBM pathological markers TDP-43, phosphorylated TDP-43, and p62 all coexisted with intensively stained key subunits of mitochondrial oxidative phosphorylation complexes I-V in the same skeletal muscle fibers of patients with IBM. Further immunoblot analysis showed increased levels of TDP-43, truncated TDP-43, phosphorylated TDP-43, and p62, but decreased levels of key subunits of mitochondrial oxidative phosphorylation complexes I and III in IBM patients compared to aged matched control subjects. This is the first demonstration of the close association of TDP-43 accumulation with mitochondria in degenerating muscle fibers in IBM and this association may contribute to the development of mitochondrial dysfunction and pathological protein aggregates.